Feline leukemia virus (FeLV) is an exogenous type C retrovirus of the Retrovirdae virus family. It is associated with multiple immunosuppressive diseases specifically with the lymphoreticular disease, including lymphosarcoma, leukemia, aplastic anemia, myelodysplasis and feline acquired immunodeficiency syndrome Hardy et al., Cancer Res. 36:582, 1976; Hardy Feline Leukemia Virus, Hardy, Essex, McCelland, eds. (Elsevier/North Holland, 1980), pp.3-31; Hoover, Rojko, Olsen, Feline Leukemia, Olsen, ed. (CRC Press, Boca Raton, Fla., 1980), pp.32-51; Hardy and Essex, Prog. Allergy 37:353, 1986). FeLV isolates are divided into three subgroups A, B, and C based on their interference and neutralization patterns (Sarma et al. Virology 44:352-358 (1971); Donahue, P. R. et. al. J. Virol. 66:722-731 (1988); Jarret, O. et. al. Int. J. Cancer 21:334-387 (1978). FeLV-A is found in every isolate in nature either alone or in combination with B and C subgroups and is considered to be the subgroup most responsible for viremia and the latent carrier state. FeLV-B is found in about 40% of all infections whereas FeLV-C is found in only 1% of infections and occurs in combinations with B and A subgroups. Because FeLV-A demonstrates a more restricted cell tropism in vitro and tends to be less pathogenic, the presence of subgroup A in all infections makes it the obvious target for prevention of FeLV infection (Loar, A. S. Vet. Cl. N. Amer. 23:193-211).
Pharmaceutical compounds that will eliminate or control virus replication once the virus is introduced in cats have not been well tested; however, several preventative vaccines have been developed. FeLV vaccines are sold under at least 8 different trade names including at least 3 combination products from 4 different manufacturers. The product tradenames include: Leukocell and Leukocell 2 (Pfizer), Leukogen (Virbac), Gentivac (Schering(Coopers), RM Leucat (Rhone-Merieux/MERIAL), Fevaxyn (Schering/Solvay), FeloVax (Fort Dodge), and VacSYN/FeLV (Symbiotics). These vaccine preparations include infected cell extracts, whole virus preparations, and recombinant envelop protein subunit vaccines. In addition to these commercial vaccines, there are several disclosures that describe other possible methods for immunization against FeLV including treatments with recombinant derived FeLV peptides alone or in combination with attenuated virus or proviral DNA preparations (U.S. Pat. Nos. 4,701,416, 4,876,089, 5,152,982, 4,789,702, EPO 0247904, PCT U.S.85/02319), virus vectors expressing FeLV gene products (U.S. Pat. Nos. 4,957,865, 5,324,664, PCT U.S. Ser. No. 88/02816, GB90/00116, U.S. Ser. No. 92/08427), peptide vaccines containing smaller components of full length gene products (U.S. Pat. Nos. 4,663,436, 4,794,168), self-assembled replication-deficient virus particle production, and vector produced non-replicative virus particle production (PCT U.S. Ser. No. 93/09070).
Despite the variety of FeLV approaches to vaccine development and utilization there are still important and pertinent features that the present preventative or therapeutic treatments do not provide. None of the vaccines utilize an antigen or vaccination method that allows for cross protection against all field isolates and subgroups nor do they include components that provide protection against other immunosuppressive or immunodeficient viruses such as FIV or FIPV. Vaccines, which use non-purified virus or infected cell material have inconsistencies in the amount of virus-associated material that exist in each vaccine preparation. As a consequence there is variability with these vaccines in both delayed and immediate site reactions. In addition, retroviruses are notoriously low producers in cell culture and are relatively unstable in unprocessed or non-cryopreserved forms, which contributes to limited storage periods of FeLV components in manufacturing. As a consequence the FeLV is often the limiting antigen when attempting to develop combination vaccines with other infectious disease agents of felines. In general, there is also an inability to determine and to discriminate subgroups A, B and C within the vaccine and manufacturing material. Because all existing FeLV vaccines on the market are inactivated (killed) preparations, two and sometimes three doses are recommended for active immunization of cats. Because of these limitations within the present commercial products and continued demands by the clinician for managing and controlling immunosuppressive disease there is a need in the art for improved methods for immunization against FeLV and associated disease.
The present invention is provided to address all of the above needs. In particular it provides a FeLV vaccine that cannot only deliver an efficacious dose of FeLV in a convenient administration, but can also be manufactured in a more consistent manner than previous art. In addition, the invention described here is derived from a new isolate of FeLV (BTI-FeLV-A) taken from a cat in Fair Oaks, Calif. This virus is subgroup A has not been described before and represents a virus isolate that has evaded or is not controlled by current vaccination programs.